Meropenem Valproate

Meropenem reduces plasma valproate concentrations, affording two mechanisms for an increased risk of seizures in patients with epilepsy, epileptogenic effect of meropenem, and loss of antiepileptic action of valproate [46, 47, 48, 49, 50, 51, 525]. In 39 patients who took valproate and meropenem valproate plasma concentrations fell in aU patients within 24 hours by an average of 66% [53 ]. 

VALPROATE ERTAPENEM, MEROPENEM i valproate levels Induced metabolism Monitor levels... 

Panipenem/betamipron dramatically reduced the valproate serum levels of 6 patients. Imipenem and meropenem have similar effects and seizures have occurred when they were given to patients taking valproate. Ertapenem is predicted to interact similarly. 

A report describes two patients whose valproate levels fell when meropenem and amikacin were given. The first patient had heen maintained on intravenous valproate 1.2 to 1.6 g daily with valproate levels of between 50 and 100 mg/L. Two days after the addition of the antihacterials the levels had halved, and after 3 days of subtherapeutic levels, phenytoin was substituted for valproate. The other patient experienced a drop in valproate levels from 44 mg/L to 5 mg/L within 24 hours of being given meropenem, despite being given greater doses of valproic acid. Other reports " describe reductions in valproate levels in several other patients when they were also given meropenem three of them developed seizures. . ... 

Although there is only an isolated report of an interaction between valproate and imipenem, there are now several reports of the interaction between valproate and meropenem or panipenem. Seizures or increased seizure frequeney have been reported. It would therefore seem prudent to monitor the valproate levels in any patient also given carbapenems, being alert for the need to increase the valproate dosage, or to use another antibacterial, or an alternative to valproate. Carbamazepine and phenytoin did not interact in the above reports. The manufacturers of ertapenem have no reports of an interaction on their files, but prudently warn about a possible interaction with valproate because of the interactions seen with other carbapenems. 

HobaraN, HokamaN, Ohshiro S, KameyaH, SakanashiM. Possible mechanisms of low levels of plasma valproate concentration following simultaneous administration of sodium valproate and meropenem, Biog Amines (2003) 17,409-20. 

Carbapenems An old Chinese man with epilepsy had seizures when meropenem was added to treatment with valproate [407 ]. In a retrospective study of six critically ill patients taking valproate who concurrently received meropenem (n = 4), imipenem (n = 1), or ertapenem (n = 1) mean plasma valproate trough concentrations fell by 58% and estimated mean valproate clearance increased by 191% compared with values obtained while they were not receiving a carbapenem five patients had generalized seizures during concurrent valproate -b carbapenem treatment, including two with no prior history of seizures [408 ]. Meropenem is an enzyme inducer. Because of this pharmacokinetic interaction, concurrent use of these medications should be avoided. 

Santucci M, Parmeggiani A, Riva R. Seizure worsening caused by decreased serum valproate during meropenem therapy. J Child Neurol 2005 20(5) 456-7. 

Spriet I, Goyens J, Meersseman W, Wilmer A, Willems L, Van Paesschen W. Interaction between valproate and meropenem a retrospective study. Ann Pharmacother 2007 41(7) 1130-6. 

Yoon H, Kim D. Unusual drug reaction between valproate sodium and meropenem. Int J Clin Pharm 2013 35 316-8. 

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